Goals for the immediate future for this project are: 1) to prepare H3-GnRH with specific activities greater than 2.0 Ci/mMole; 2) to identify the high specific activity tritium-labeled derivative which possesses GnRH biological activity; 3) to isolate and identify H3-GnRH metabolites entering the blood and urine of rhesus monkeys and rats; 4) to determine the tissues involved in the peripheral metabolism of H3- GnRH and the specific sites of peptide cleavage involved; 5) to study the metabolism of H3-GnRH by the pituitary, in vivo and utilizing an in vivo perfusion system; and 6) to utilize tritium labeling of hypothalamic and portal blood extracts to identify the GnRH structure in several species. The increasing recognition of the importance of peptides in human physiology, health and disease has provided a renewed impetus to the study of their identification, synthesis, measurement and metabolism in the fields of endocrinology, hypertension, allergy and gastroenterology, to mention a few. The studies described herein provide a unique approach to the study of the metabolism, measurement and identification of one such peptide, GnRH. It is hoped that a complete understanding of the mechanism of GnRH disposal in the pituitary and after entering the peripheral circulation will make it possible to design GnRH analogues which can be more effectively utilized in the control of reproductive function. It is also hoped that such studies will serve as a prototype for the elucidation of the role of other peptides in physiological processes.